The aims of this investigation are directed toward an understanding of the mechanisms and control of membrane associated electron transport processes in M. phlei, the mode of action of the antitubercular drug isoniazid (INH) on such processes in mycobacteria, and the biogenesis of the mitochondrion in C. fasciculata. Studies will be performed to elucidate the role of water soluble complex S(G-25) containing MK-9(2H), phospholipid, and protein, and a low molecular weight C fraction (which can be replaced by polyvalent anions) in restoring NADH oxidase activity to irradiated electron transport particles (ETP) in M. phlei. The NADH dehydrogenase will be purified, characterized, and the role of the above mentioned factors, as well as the effector NAD ion will be studied to reconstitute and characterize the electron transport chain prior to cytochrome b. ETP depleted of phospholipids and MK-9(2H), and inactivated dehydrogenase will be used to characterize the insertion of these components into the natural membrane. Artifically prepared liposomes will also be used. The mode of action of INH will be studied in relation to its role in desensitizing the ETP to the effector INH. An INH resistant mutant which grows under anaerobic conditions will be characterized as to its metabolism and membrane associated energy-linked functions. INH resistant strains isolated from patients will be used to determine whether these organisms can grow anaerobically. The study of the biogenesis of the mitochondrion (mt) from C. fasciculata will include determination of the proteins that are coded for by mtDNA, how cytoplasmic synthesized proteins are incorporated into the mt, the nature of the coordination between nuclear and mtDNA replication, and the nature of cytoplasmic control on mt protein synthesis.